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Low-dose Pegylated Interferon Maintenance Therapy Does Not Reduce Clinical Outcomes despite Persistent HCV Suppression

SUMMARY: Low-dose pegylated interferon maintenance therapy did not reduce the rate of adverse clinical outcomes of chronic hepatitis C virus (HCV) infection among patients who did not respond to standard-of-care combination therapy, even if their viral load remained suppressed. These findings from the HALT-C trial were published in the December 2009 issue of Gastroenterology.

By Liz Highleyman

In the HALT-C trial, more than 1000 participants with advanced liver disease who did not achieve sustained virological response (SVR) to standard treatment with pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (PegIntron) plus ribavirin were randomly assigned to received either low-dose (90 mcg/week) pegylated interferon alfa-2a maintenance therapy or no further treatment.

As previously reported, after 3.5 years, patients who received maintenance therapy had lower liver enzyme (ALT and AST) and HCV RNA levels, but were not significantly less likely to progress to hepatocellular carcinoma, decompensated cirrhosis (e.g., ascites, variceal hemorrhage, hepatic encephalopathy), fibrosis score increase of 2 or more points, or death.

In the present study, the HALT-C team explored whether persistent HCV RNA suppression during the trial was associated with reduced clinical outcomes. This analysis included 764 patients treated during the lead-in (standard combination therapy) phase of HALT-C and randomized to the maintenance therapy or no further treatment (control) arms.


During the lead-in combination therapy phase, 178 patients (23%) experienced at least a 4 log10 decline in serum HCV RNA.
82% of these patients achieved undetectable HCV RNA, but later experienced viral breakthrough or relapse.
This group had significantly fewer clinical outcomes, whether they were randomized to receive maintenance therapy or no further treatment (P = 0.003).
Following randomization, HCV RNA levels increased significantly in all 90 patients (100%) in the control arm and in 58 of the 88 patients (66%) receiving maintenance therapy.
Only 30 patients overall had HCV RNA persistently suppressed by 4 log10 or more during the course of the study.
Among these patients, there was no significant reduction in clinical outcomes versus participants with rising viral load.

Based on these findings, the investigators concluded, "Viral suppression by >4 log10 with full dose peginterferon/ribavirin is associated with a significant reduction in clinical outcomes."

However, they added, "Continuing low dose peginterferon maintenance therapy, even in patients with persistent viral suppression, does not lead to a further decline in clinical outcomes."

Virginia Commonwealth University Medical Center, Richmond, VA; University of Washington, Seattle, WA; Massachusetts General Hospital and Harvard Medical School, Boston, MA; Keck School of Medicine, University of Southern California, Los Angeles, CA; University of California-Irvine, Irvine, CA; University of Texas Southwestern Medical Center, Dallas, TX; National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD; New England Research Institutes, Watertown, MA: University of Colorado Denver, Anschutz Medical Campus, Aurora, CO; University of Michigan Medical Center, Ann Arbor, MI; St. Louis University School of Medicine, St. Louis, MO; University of Connecticut Health Center, Farmington, CT.


M Shiffman, C Morishima, JL Dienstag, and others (HALT-C Trial Group). Effect of HCV RNA Suppression During Peginterferon Alfa-2a Maintenance Therapy on Clinical Outcomes in the HALT-C Trial. Gastroenterology 137(6): 1986-1994 (Abstract). December 2009.



























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